Dissecting Susceptibility to Periodontitis by Using Collaborative Cross Mouse Population

Periodontal diseases are chronic inflammatory diseases, which result in the breakdown of the supporting tissues of the teeth. Previous Epidemiological studies have suggested that susceptibility to chronic periodontitis is controlled by host genetic factors. The collaborative cross (CC) is a novel, unique and genetically highly diverse mouse population, which was proposed by the complex trait consortium (CTC) for studying systems genetics, including host susceptibility to infectious and chronic diseases. The CC lines derived from eight inbred mouse strains through a mating scheme, and the lines are mosaics of the founders and each carry different recombination points.

Objective: to determine the phenotypic response of inbred and CC mouse population to periodontal bacterial challenge using the experimental periodontitis model.

Methods: Initially, we studied age matched male and female mice of different inbred strains (BALB/CJ, DBA/2J, C57BL/6J and A/J), which were orally infected with Porphyromonas gingivalis and Fusobacterium Nucleatum. The infection was repeated three times at 2 day intervals. Six weeks following the final infection, the maxillary jaws were harvested and analyzed for alveolar bone loss using microCT technique. Later on, we have applied the same protocol on 5 lines from the CC mouse population.

Results: BALB/CJ mice were susceptible while DBA/2J, C57BL/6J and A/J were significantly resistant. Subsequently we found 2 susceptible lines and 3 resistant lines out of the 5 CC lines. Broad-sense heritability of the trait in all mouse lines was calculated and found to be 0.91, which is very high.

Conclusions: Here, we have shown that mice with different genetic background responded differently to periodontitis. The high rate of estimated heritability indicates that the variation in host susceptibility to the disease is, mainly controlled by genetic factors. These results have opened the possibility of exploiting the oral infection mice model to identify quantitative trait loci (QTL) underlying the disease.